Abstract
Protein regulation and protein-protein interactions are fundamental to the function of the cell, governing processes such as growth, differentiation, metabolism, and immune responses. A critical aspect of this regulation is phosphorylation, where kinases and phosphatases function to add and remove phosphate groups from proteins, respectively. The interplay between these enzymes maintains proper phosphorylation states essential for cellular signaling and homeostasis.
At the heart of these interactions is SHP2, a protein tyrosine phosphatase essential for dephosphorylating tyrosine residues on target proteins, thereby effecting signal transduction pathways. Critical to the function of SHP2 is its activation by bis-phosphotyrosine containing peptides, which upregulate SHP2 activity upon binding. Through examining both natural and mutant forms of SHP2, this dissertation bridges our understanding of its regulation and dysregulation, offering a comprehensive view of SHP2 activation mechanisms.